Implementation of tofersen Expanded Access Program in the US, the cumulative experience of six academic centers

Document Type

Conference Proceeding

Publication Date

11-15-2023

Publication Title

Amyotroph Lateral Scler Frontotemporal Degener

Keywords

acetarsol, tofersen, alternative medicine, amyotrophic lateral sclerosis, best practice, clinical trial, compassionate use, conference abstract, Food and Drug Administration, human, interventional radiology, intrathecal drug administration, patient visit, phase 3 clinical trial, United States

Abstract

Background: Expanded access programs (EAP) are pathways for patients with a serious condition, like ALS, to access investigational products outside of a clinical trial when no alternative therapy option is available. These programs were very common in HIV and oncology but are relatively new to the world of ALS therapeutics. In July 2021 Biogen, right after enrolling the last participant in the phase 3 study of tofersen (Valor), launched its expanded access program for tofersen. Objective: The objective of this presentation is to describe the experience of six academic centers in the United States administering tofersen EAP from July 2021 to June 2023. We discuss the challenges and the infrastructure needed to implement such a program. Methods: Each institution, submitted the tofersen EAP to the FDA under an investigational new drug (IND) application for a single patient and/or an intermediate-size population. Once FDA approval was granted, the EAP protocol was submitted to their respective institutional review board (IRB). Key inclusion criteria included the patient ability to undergo intrathecal drug administration and the presence of weakness attributable to SOD1 ALS. Tofersen was provided by Biogen at no direct cost. Research staff time was used for regulatory submissions to the FDA and IRB. Research staff and investigator time was used for recruiting, consenting, scheduling, safety, and efficacy monitoring. Research pharmacy was used for IP preparation and dispensation. Safety labs, patient visits, and IR/ bedside administrations of tofersen were billed clinically and/or internally funded. Results: Thirty-three patients from six US ALS centers were enrolled, 55% with SOD1 pathologic mutations, 36% likely pathologic and 9% VUS. At enrollment, the mean age was 54.6, mean disease duration was 46.3 months, mean FVC/ SVC was 81.6 %. About 40% were submitted as a single patient EAP but most patients were eventually reconsented as part of an intermediate size EAP. Tofersen was administered intrathecally by the investigators or by interventional radiology. The schedule of events and safety and efficacy monitoring varied considerably from site to site. Operational costs also varied per participant across the different sites which were largely undertaken using local institutional or philanthropic support. Discussion: The tofersen EAP represented a unique opportunity for SOD1 ALS patients to access a potentially lifesaving treatment outside of the Valor trial. It was highly anticipated by patients. We present different operational models used by the six busy ALS centers with variable use of staffing resources, funding, and outcomes monitoring. As EAPs in ALS become more widespread, there are benefits to the establishment of best practices across sites to balance expedited access of these important therapies with the acquisition of invaluable safety and efficacy data. A consistent funding mechanism through pharma and academic partnership is one potential strategy to accomplish these goals.

Volume

24

First Page

217

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